mardi 26 août 2008

Is the first neuroleptic at the origin of aliberation of the madman or a social dismissal?

Dr. Séverine Massat
03.88.67.03.19
www.graphein.fr
severine.massat@gmail.com

“Is the first neuroleptic at the origin of a liberation of the “madman” or of a social and psychiatric dismissal?”

« The current world doesn’t know how to deal with those who are not - or no longer competitive: the elderly, the unemployed, the handicapped, youngsters from poor neighbourhoods, the mentally ill... The old couple of madness and misery is here again, under our very eyes, in the street. Madmen, delinquents and criminals find themselves once again under the same roof, the prison’s (roof) that is, like at the time of Louis XIV»[1]

Largactil first antipsychotic medicine was launched on the market in 1952 by the firm Rhône-Poulenc. Whether in histories of contemporary medicines or in articles specialised in the history and developments of psychiatry, this medicine is unanimously described as "revolutionary" and that at several levels.
At the level of psychiatry itself, it inaugurates an almost non-existent psychopharmacology so far. At the level of the asylums personnel, Largactil calms down maniacs’ febrile outbursts, gives catatonics their speech back and allows dialogue with the nursing staff. At the level of the psychiatric institution itself, the first neuroleptic, then products with “delayed effects” will allow the patients to go out of the hospital where they were condemned, until then, to live their entire lives. At the level of the individual himself and of his freedom, the debate has started between partisans of the chemical therapy and those who speak about a chemical straight-jacket which maintains in a different way, the patient in captivity. At the level of the pharmaceutical industry in France then in the world, a prosperous market is developing with psychotropic neuroleptics and antidepressants and anxiolitics, and never seems to have to stop its growth. At the level of the epistemological reflection itself, as far as the perfecting and the generalisation of medicines which act on the brain are used in fine to modify behaviours and thoughts[2].
To go back on Largactil as first case: on its perfecting, the conditions of its market launch and its experimentation, allows us to question a phenomenon which has incessantly become more and more marked since the 1950s: the medicalisation of mental illness but also the psychic suffering in general, with the ontological shifts which we are witnessing as a trivialisation of medicines becoming “health products” and the falling apart of the categories of psychiatric diagnoses with the generic notion of "mental health" which tends to merge with the pursuit of well-being.
How does our society face the mental illness today? What did it inherit from the model which psychiatry inaugurated with the generalisation of psychotropic medicines (neuroleptics then antidepressants)? Further, our work wishes to show a paradox inferred by the use of psychotropic drugs. By freeing the practitioners and the psychiatric therapeutic practice, the generalisation of mental illnesses chemotherapy resulted in the reduction of our tolerance threshold towards it, and of what we, today, begin to consider again as deviant and dangerous behaviours which the drama of Pau crystallizes, as well as in an increasing assimilation of the mental illness to a social handicap[3]. To return to the origin of these questions by examining the case of Largactil, is the heuristic tool that we choose.


1. Largactil can fulfil a desire

« Nowadays when psychotropic medicines abound, it is difficult to imagine the desert that was (...) the psychiatric pharmacopoeia »[4]

We can, by cutting the events coarsely, consider that there is one transitional moment for our society in the way it deals with its "madmen": before and after the Liberation. Up until the liberation, society wants to protect itself from madness because it frightens it; madness is a menace to the good functioning by threatening the order[5]. After the Liberation, we want to treat, care for the madman, one cannot tolerate anymore that he is excluded or even eliminated from society after the experience of camps, the eugenic and hygienic drift, and the slaughter of mental patients by malnutrition[6]. The history of the perfecting of Largactil and its success joins in this desire of society in general and of the post-war psychiatry, it will respond extraordinarily by giving a new medical and scientific legitimacy to psychiatry which wants to be from then on “biologic”. Largactil gives society a new and convenient way to converse with madness and to bring back to a "normal" life those who were excluded from it until then.
At the time of the discovery of the first medicine treating psychosis and schizophrenia in particular, the psychiatric pharmacology had hardly progressed since the invention of barbiturates at the beginning of the XXth century. Since the end of the 1930s, we only have unpredictable treatments at our disposal to treat nervous pathologies like tonics (tea, coffee), remineralisation therapies, and painkillers against the excitement outbursts. To treat emotional trouble, we use opiates, faradisation, and physical exercise. With the perfecting in 1938 of the electric shock treatment, we try to provoke sedation or stimulation by means of a coma or of a convulsion. We use sleep therapy to take out the schizophrenic of his frenzy in which he lives like a recluse. The French psychiatry is dominated by Henri Ey and Jean Delay (1907-1987) who takes up his duties at Saint Anne at the end of the 1930s, obtains the chair of the clinic for mental illnesses, manages L’Encéphale in 1946 and introduces the seminars of Lacan.
Delay pronounces the opening conference of the first world congress of psychiatry which takes place in Paris in 1950 in which he declares: « if the word of cure, so serious by the hopes that it creates, must only be said with restraints, it is not forbidden any more [7]» the intern optimism of psychiatry contrast with the everyday life in an asylum described in the review Esprit which titles in 1952: « Misery of psychiatry ». Nevertheless, a new wind blows on the discipline and de-alienate the madmen becomes a mobilising subject, stemming from camps as well as from methods of shock. At the end of the 1940s, the electric shock treatments are applied to the most diverse mental confusions, their efficiency weakening as the treated states get closer to the normal state, without knowing why or how they work. It is thus in this particular post-war climate that Largactil, which means “wide action”, makes its entrance on the market with indications as vast as vague[8].




2. Largactil in psychiatry: the history of a “re-appropriation”

February 13th, 1952 appears in La presse médicale an article jointly signed by Henri Laborit, Robert Alluaume and Pierre Huguenard, regarding a vegetative stabiliser: the compound 4560 RP (for Rhône-Poulenc). This text of harmless appearance which comes straight from previous works concerning the properties of Diparcol that Laborit and Huguenard use in anaesthesia for its potentiating properties of general anaesthetics constitutes a major event. Indeed, it is the first time that we can read concerning 4560 RP or chlorpromazine, a molecule synthesized by laboratories Specia (subsidiary of Rhône-Poulenc), its promising interest in the psychiatric field. This compound arises from works of Laborit and Huguenard which mix substances, whose principal role is to protect patients from post-operative shock and which, in use, turn out to show potentiating effects of the anaesthesia. It is as such that the product is proposed to experiment by the laboratories Specia which present the product as a “neuroplegic medicine: elaborated according to the concept of Laborit”. Its trademark reveals the extent of its therapeutic applications: it is named medicine of wide action and is first launched on the market with indications all over the place as the advertising iconography used for its promotion with doctors suggests. The events, which mark out the launch of Largactil on the market and its experimentation in psychiatry building it as "neuroleptic” medicine, are spread out over a few months only, a few months that were enough to radically change psychiatry. We find a series of articles which follow this first case article of Laborit, Alluaume and Huguenard, concerning the product’s tests. This series of articles which followed each other very quickly shows to what extend the chlorpromazine (4560 RP) is the object of intense tests in association with other medicines such as barbiturates in sleep therapy, then alone.
Whether it is about the article of psychiatrists from the Val-de-Grâce convinced by Laborit to test the medicine on obsessive agitation, or about Renée Deschamps' article which appears in La presse médicale on June 21st, 1952, they deal with the use of 4560 RP in association with other products and testify of the influence of Laborit’s techniques in its experimentation. The parallelism between the shock suspensive techniques of Laborit and the methods of psychiatric shock which are finally based on the same regulating centres is disturbing and would deserve an in-depth study that would show this major conceptual passage, from methods of shock to methods of disconnection. We understand by the success of shock therapies, that chlorpromazine is used for the first time by psychiatrists of the Val de Grâce on a patient who suffers from violent obsessive attacks. Treated by electroshock treatments repeatedly without durable results, the administration of chlorpromazine calms the patient down immediately; he is considered cured after three weeks of treatment. Andrée Deschamps tests the molecule on the model of induced hibernation developed by Laborit and Huguenard, to obtain sleep therapy. The tests which are reported concern sleep therapy of 8 days, administered on 4 different pathologies: a melancholic and anxious patient, a maniac, a patient suffering from dementia of influence, and finally a patient with hallucinations. She notes that: «the central action of 4560 RP, which was interpreted by Laborit as a synaptic interception between the corticality and the diencephalon realising in a way a pharmaco-dynamical lobotomy that allowed us firstly to obtain a de-conditioning (...) and secondly to bring the patient to the sleep with very limited doses of barbiturates [9]». If the phenomenon of potentialisation of barbiturates since the works of Laborit was predictable, it is the effect of de-conditioning that Laborit already noted about its “lytic cocktails” and that he tries to find as central effect with 4560 RP, which is remarkable. The patients of Deschamps stay in a drowsiness (effect of Phénergan), in a sort of detachment towards their entourage, or even indifference.

3. Chlorpromazine tested alone

«The behaviour of the treatment we have adopted is rather different from the techniques proposed before, since the product was used alone, without trying to achieve a sleep therapy or hibernation, and without association with hypnotics or painkillers [10]».

4560 RP is tested alone for the first time by the Professor Jean Delay and his assistant at Saint Anne Pierre Deniker, alerted by his brother-in-law who attended a conference of Laborit at the Val de Grâce. The originality of the tests they carry out is double. Their method seems to distance itself at first from Laborit’s, because they use the product neither in association, nor for its hypnogenic properties. It distances itself from psychiatric treatments of the time which consist mainly of sleep therapy and electroshock treatments, to better come back to notions that are very close to those developed by Laborit. As the latter showed it about shock syndromes (post-operative disease and traumatic shock), Delay and Deniker mention that the knowledge of the shock therapeutic modes of action which notably act by stimulation by provoking a state of crisis and their integration in the general pathology, lead to search if reverse means do exist. They look for means aiming to put to rest or to interrupt the reactional processes which in some cases can constitute the substratum of the disease, if not the disease itself. Delay and Deniker, in the same way as Laborit, distinguish between, on one hand, the disease considered as localised lesion, and on the other hand the reactions of the body to an aggression which can engage it in the release of pathogenic processes. Just as Laborit tries to subdue the post-operative or anaesthetic shock, Delay and Deniker, by administering chlorpromazine alone, try to obtain mechanisms of disconnection or exclusion. In the case of surgical or anaesthetic shocks, the disconnection sought after is the one of the vegetative or peripheral nervous system, to avoid a mainly vascular crisis state. In the case of psychiatric pathologies, this time it is about obtaining a central disconnection: a neurolepsy or nervous suspension. This term of “neurolepsy” which Delay and Deniker propose, arises from the concept of psycholepsy developed by Pierre Janet which indicates this drop of nervous tension or neurovegetative which conditions partially the psychological tension corresponding to the clinical action of medicines, producing essentially a relaxation. This neurolepsy is obtained by using chlorpromazine in continuous and prolonged cures, without any other associated medication. We obtain then a visible indifference and the delay in the response to outside stimulations, the emotional and affective neutrality, the decrease of initiative and concern, without any change in the guarding consciousness or intellectual faculties: such is the psychic syndrome of chlorpromazine.

4. The silent revolution of asylums

« The concept of neurolepsy opposes the concept of shock (…). In neurolepsy, on the contrary, it is not a general mobilisation of the defences that we try to produce, but a sort of demobilisation, not an alarm reaction of the nervous system, but a reaction of relaxation. So is established in the body a regime of truce which opposes to the regime of alarm provoked by the therapeutics of shock [11]».

To understand this haste to test Largactil and to measure on the field this revolution of the asylum world, we refer to one interview with Daniel Ginestet in internship at the Saint Anne hospital in 1952, on a work by Jean Thuillier, also in Saint Anne in 1952 in Pierre Denicker's service and on two works by Delay and Deniker: a work on the techniques of shock of 1946, the second on new psychotropic medicines of 1961[12]. We shall also base ourselves on more recent works of Toine Petters and Stephen Snelders[13] and Patrick Coupechoux[14].
What is striking and recurring in the majority of stories which describe the state of psychiatry and the asylum institution before the introduction of Largactil is its extreme destitution. All assert that there was no medicine specific to madness. What we practice are cures of barbiturates with which we literally knock out the patients by administering massive doses to which they become dependent, or cures of electroshock treatments and insulinic comas. These cures are repeated: a cure of Sakel needs from 40 to 60 comas, with a frequency of 5 comas per week to treat a schizophrenic. As Daniel Ginestet explains it, the initial aim of these treatments is to have peace. The profession of psychiatrist and psychiatric nurse is difficult, the patients are often violent. « It was not a nice gift, when we received a maniac who during weeks was going to scream, scold his neighbours, whom we were obliged to put in a straightjacket or even attach to his bed with straps, whom we needed to feed with difficulty and to keep clean[15] ».
Ginestet, who works in Saint Anne in 1953, describes a hospital radically changed by Largactil. The pavilion of the agitated is quiet, nurses and psychiatrists no longer fear their patients who speak, and the medicine brings a double revolution. It cures patients who will be able to go home and this all the more easily with the perfecting of the cure said with delayed effect, and it allows the return of speech: speech of the patients and dialogue with the doctor. The neuroleptic cure allows continuity where the electroshock treatment offered only sequences. The disruption that it entails is at first spectacular observations with simple or even crafty means. Nevertheless, what is new in the experimental method of Delay and Deniker is a systematic approach, with a selection of patients on whom the product is tested as shown it the series of articles that they publish.

The first publication is made on the occasion of the centenary of the Medical psychological Society. In the two months following this first note, 5 communications are published bringing detailed indications regarding the states of excitement and agitation, the treatment of states of confusion, the treatment of psychoses and biologic reactions observed during the treatment. This set of works allows identifying three important notions. First of all, the efficiency of chlorpromazine administered alone and in a prolonged way. The clinical description of a psychomotor syndrome characteristic of the psycho-physiological action of chlorpromazine: «When drowsiness resolves, the patient seems, at first sight, normally awake: in reality he is in a characteristic psychic state and which never misses (…) He rarely takes the initiative of a question, he does not express concerns, desires or preferences. He is usually aware of the improvement brought by the treatment but does not express euphoria [16]». It is precisely this syndrome of emotional neutrality and affective indifference that is going to define the neuroleptic syndrome. The third notion identified from the treatment is the therapeutic action of the product in psychoses: it is not a symptomatic treatment reducing agitation, nor sedative of anxiety, it is about a real chemotherapy of psychoses that it reduces sensibly: «The results obtained in this case seemed worth being underlined, because they allow to infer that this medicine does not act as a simple sedative for agitation, but it possesses a more complex central action, confirmed by biologic reactions [17]». Not only the patients are selected but Ginestet watches their state three times a day by measuring their blood pressure, their temperature etc. Very quickly, we obtain something more than the sedation, an improvement of states of confusion and Ginestet presents to Jean Delay, during weekly meetings at Saint Anne, the first maniac patient cured. Very quickly also, Deniker notices these effects and writes a synthesis. What for Laborit constitutes an effect of disinterestedness, becomes in the terms of Deniker an ideological and emotional indifference. The cure of chlorpromazine which at first is used only in the critical states is soon applied to the chronic deliriums in Saint Anne's services, but also by Henri Ey in Bonneval with very timorous dosage because the side effects of an unknown medicine are feared. Deniker becomes the promoter of Largactil; he leaves with his samples for Austria, Germany and all Europe. From 1952 the hospitals of the provinces have samples, like the hospital Sainte-Marie de l' Assomption in Clermont Ferrand. Is it not a revolution to see this hospital, whose medical tradition was based before the war on mistrust towards all drugs, use this new medicine the same year a scientific communication made it known?[18]

If Largactil seems to spread in psychiatric hospitals like a powder trail, its entry in the United States happens later. Heinz Lehmann introduces it at first in Canada and shares the Albert Lasker price in1957 with Laborit and Deniker, for the introduction of the medicine in the United States[19]. If the introduction of Largactil to treat psychoses was doubtlessly the object of hesitations, the organisation as from 1955, of a colloquium entirely dedicated to chlorpromazine under Jean Delay's presidency, reveals the disruption of the world of psychiatry in the 1950s. This disruption does not escape Jean Delay’s scrutiny and he underlines from the introduction session, that the presence of specialists and the multitude of interventions on the product’s use, are the sign of the interest attached to neuroleptic cures. However, chlorpromazine is not a psychiatric panacea. Delay and Deniker notice that it is far from being as effective in the depressive syndromes as in the syndromes of excitement, even if it remains effective in the syndromes of simple or reactional depression, the experiment shows that unlike the electroshock treatment, the new neuroleptic-chemotherapy supplies in the endogenous depressions only disappointing results and is not exempt from side effects. But if psychiatrists themselves widely participate in the success of the product, the asylums nursing staff also plays a role in its generalisation in hospitals.

5. Largactil: liberation of the patients or the nursing staff ?

“Everybody admits easily that neuroleptics have made decibels drop in a service. It is true that another image interferes with the one of peace, which is the image of a chemical straightjacket maintaining the patients in a habitus of inertia and sometimes rather horrible and caricatured reduction to a mindless state[20]”.

There are few indications on how the use of Largactil then chemotherapy in general in psychiatric institutions has spread out. The recent work of Toine Peeters and Stephen Snelders who examine the path of the product in a Dutch asylum or of a team of practitioners and historians from Lyon, is a precious help to show that beyond a dichotomy between partisans of biologic psychiatry or the psycho-genetic origin of the mental illness, the use of this product has played a much more complex role, even contradictory with what has been written so far. What is striking in Peeters and Snelders work is the pressure applied by the nursing personnel (nurses) to use this product despite its important side effects like painful skin irritations, kynestesic troubles or from Parkinson’s disease, or also a general hypotensor effect which can be fatal to some patients. As the authors underline it rightly, the use of neuroleptics then the generalisation of these medicines to cure mental illness and today psychic suffering in general (from anxiety to depression), reflects more than a medical commodity; “they also reflect developments and transformations in the science and art of healing as a cultural process[21]”.
Toine Peeters and Stephen Snelders base their analyses on studies of the introduction of Largactil by the team of Frederik Tolsma responsible for a psychiatric institute, the Maasoord in the Netherlands. Tolsma begins the use of Largactil in 1953, 9 months after its first publications by Delay and Deniker. He is familiar with sleep therapies using antihistamines as sedatives (Antergan and Phenergan) to treat agitated patients. His initial idea is to reproduce the technique of induced hibernation developed by Laborit, despite the absence of expertise linked to this particular technique of internal cooling. His team begins the experimentation of Largactil alone and in association with other sedatives. The same way as in Saint Anne, the team notes a type of new sedation. After a few days of treatment with this product, the team obtains a strange sedation, closer to a general detachment than to an actual sleep, which it compares to an effect of pharmacologic lobotomy. It allows patients hospitalised for several years to access a form of active therapy in which communication with personnel becomes possible. One of the nurses who work with “chronic” patients notes a radical change of atmosphere in her ward, aggressiveness replaced by peace and quiet. By calming agitated patients, i.e. the terror of the institution, the use of chlorpromazine decreases drastically the use of other sedatives administered until now. Despite these very positive effects of the Largactil treatment, Tolsma’s team shows criticism. It notes that the neuroleptic cure brings symptoms back and it presents bothering side effects such as allergic troubles, low blood pressure. Peeters notes also that in some other asylums, the introduction of Largactil is not spontaneous but rather strongly pushed by medical representatives from the laboratories Specia, who offer free samples and present the product as the ideal medicine to gain peace, quiet and stability of the nervous system, which sometimes seduces more the psychiatric nurses than the heads of services themselves. Peeters and Snelders note in that sense: “in offering both an effective means of chemical restraint and a therapeutic tool that could produce visible recoveries in even the most desperate cases, chlorpromazine boosted the moral of the staff. The fact that chlorpromazine could also produce visible side effects did not seriously affect their enthusiasm. Nurses were already familiar with the occurrence of the side effects of the conventional somatic therapies in general (…) such as insulin coma therapy and electroshock therapy. They considered management of side effects as something that came with the job[22]”. The position of Peeters and Snelders is that the nursing teams have played a central role in the setting up of a routine chlorpromazine cure by planning the cure to limit its side effects whether it is the administration of the medicine orally, to avoid skin irritation effects or wearing a hat to protect patient from photosensitivity induced by the molecule. The setting up of the Largactil cure under the personnel’s pressure has forged the reputation of the chemical treatment as more human, in the way where it becomes an access to social and psychotherapeutic therapy. Peeters and Snelders note that chlorpromazine is in no way considered as a new form of chemotherapy of the soul, but as a “state of art” of sedation adaptable depending on the cases. Tolsma himself sees the treatment as catalyser in the curing process. We don’t hesitate anymore then to administer the product with high dosage (more than 2000 mg per day) considering the presence of secondary side effects of Parkinson type as a clinical indicator of the optimal effect of the treatment.
This point is also very important in the success of chemical therapies, as we have shown in the advertising illustrations of Largactil; the treatment is firstly presented by the industry as a mishmash of a medicine with indications as vast as non specific, it is used as soon as 1953 and with its success in psychiatry, the industry builds it a proper identity by differentiating it from regular sedative treatments. This is this will of the industry to build a therapeutic ground from the molecule and not from the clinic that is striking in this case, and which explains that for a long time (until the 1960s at least) we defined its action by one of its side effects like the extra-pyramidal troubles. In 1968 at the occasion of the 15th anniversary of the introduction of the molecule in the Netherlands, Tolsma reveals that the new remedy is the object of a phenomenon of accustom with patients the same way as with doctors and nursing staff of psychiatric hospitals[23]. According to him, the long-term use of neuroleptics must be correlated to the decrease in tolerance of the society toward agitated patients of psychiatric hospitals. The evolution and the actual situation had to unfortunately agree with him.

6. Paradoxical successes of psychiatric chemotherapy

We have seen that the construction of the first neuroleptic by psychiatry has appeared at a very specific moment, the post-war era: where imprisonment, exclusion of mental patients was not tolerable any more. The experimentation and the “success” of the neuroleptic cure have brought a great boost to psychiatry and this in different ways. First, by legitimising it: proclaiming to be from biology, it integrated the seraglio of medical science. By permitting the access to speech and dialogue, it endorsed humanism of psychotherapy and analytic cure. Lastly, at the institutional level itself, it allowed to de-alienate the crazy, get the sick out of the asylum, even if this term was replaced by psychiatric hospital. What has happened since?
We witnessed since Largactil an increase in availability of medicines for mental illness and psychic suffering in general. The first antidepressant, made from the same molecular family as chlorpromazine (the phenothiazines) is launched on the market in 1957 by Ciba, followed by anxiolitics. The pharmaceutical laboratories were faced by an enormous market, and without really finding new products they adjusted the side effects of molecular families that they knew well (tricyclics, IMAO, IRS). But the success is not without a set back.
By offering this pharmacologic tool to psychiatry, it leads the latter to define mental illnesses on the basis of effects provoked by medicines. The situation brings today psychiatry in a theoretical dead-end in which a symptom becomes the nosographic description of the entire illness, without us knowing, even if neurosciences claim the contrary, where the mental illness comes from. It allowed also patients to get out of the asylum, since with delayed effect products, a monthly injection is enough. But there also, it results in the paradox that the patient is taken care of by psychiatry only in a crisis situation, and that the first solution, if not the only one, has become the prescription of medicine. The de-alienation has become a new form of alienation, a pharmacological alienation for psychiatry itself and for the patients. The prophecy of Tolsma is become a reality, these medicines practical for the nursing personnel and finally for the entire society, lead to a decrease in our tolerance toward madness and what has become in our vocabulary the “mental health”, the “psychic suffering” and today the “psychic handicap”. These “perfect” drugs as Alain Ehrenberg underlines it induce 3 types of risks: first, an inflation of the authority position of the medical profession. Then, a pathologisation of personality traits with the creation of pathologies which we are witnessing (erectile difficulty, premenstrual syndrome, depression in a very large measure), which lead to the exclusion of the “psychic inadequate” people linked more and more to social handicapped. Lastly, the increasing difficulties to support frustrations, for lack of means to differentiate pathologic sufferings and ordinary misfortunes, can contribute in a vicious cycle, to support less and less problems without any chemical assistance.



[1] COUPECHOUX, Patrick, Un monde de fous, Seuil, Paris, 2006, p. 16
[2] WIDLOCHER, Daniel, Les psychotropes, une manière de penser le psychisme? Paris, Seuil, Les Empêcheurs de penser en rond, 1990.
[3] EHRENBERG, Alain, L’individu incertain, Paris, Calmann-Lévy, 1995.
[4] THUILLIER, Jean, Les dix ans qui ont changé la folie, la dépression et l’angoisse, Paris, Erès, 1981, 1999, 2003, p. 221.
[5] FOUCAULT, Michel, Le pouvoir psychiatrique, cours au Collège de France, 1973-1974, Paris, Gallimard-Seuil, 2003.
[6] COUPECHOUX, Patrick, Un monde de fous, comment notre société maltraite ses malades mentaux, Paris, Seuil, 2006, pp. 71-88.
[7] DELAY, Jean, Discours d’ouverture du premier congrès mondial de la psychiatrie, Paris, PUF, 1950, p. 89.
[8] Voir illustration
[9] DESCHAMPS, Andrée, « L’hibernation artificielle en psychiatrie », La Presse médicale, Paris, 21 Juin 1952, p. 945.
[10] DELAY, Jean, DENIKER, Pierre, HARL, Jean-Marie, « Utilisation en thérapeutique psychiatrique d’une phénothiazine d’action centrale élective (4560 RP) », Annales Médico-Psychologiques, Centenaire de la Société Médico-Psychologique, Paris, juin 1952, 110 (2), pp. 112-117.
[11] Ibid, p. 304.
[12] DELAY, Jean, L’électrochoc et la psycho-physiologie, Paris, Masson, 1946. DELAY, Jean, DENIKER, Pierre, Méthodes chimiothérapeutiques en psychiatrie, Les nouveaux médicaments psychotropes, Paris, Masson, 1961.
[13] PIETERS, T. SNELDERS, S., « Mental Hills and the Hidden history of Drugs Treatment Practices », In : GIJSWIJT-HOFSTRA, M. OOSTERHUIS, J. VIJSELAAR, H., Freeman (Eds), Psychiatric Cultures Compared. Psychiatry and Mental Health Care in the 20th Century/ Comparisons and Approaches, Amsterdam University Press, 2005, pp. 308-401.
[14] Op. Cit. 2006.
[15] THUILLIER, Jean, Op. Cit., p. 192.
[16] DELAY, Jean, DENIKER, Pierre, Article cité, p. 503-513.
[17] DELAY, Jean, DENIKER, Pierre, HARL, Jean-Marie, GRASSET, André, « Traitement d’états confusionnels par le chlorydrate de diméthylaminopropyl-N-chlorophénothiazine (4560 RP) », Annales Médico-psychologiques, 110 (2), n° 3, octobre 1952, pp. 398-403.
[18] BONNET, Olivier, « De l’asile à l’hôpital psychiatrique : la révolution des années 1950à L’hôpital Sainte-marie de l’Assomption à Clermond-Ferrand (1945-1965) », In : Actes de colloques : « Questions à la révolution psychiatriques », Editions la ferme du Vinatier, le 8 décembre 1999, pp. 37-54.
[19] LEHMANN, Heinz, « L’arrivée de la chlorpromazine sur le continent américain », L’Encéphale, Vol. XIX, Fasc. 1, Janvier-Février 1993, pp. 57-59.
[20] EY, Henri, « Neuroleptiques et services psychiatriques hospitaliers », In « Neuroleptiques 20 ans après », Confrontations Psychiatriques, Paris, N° 13, 1975, p. 32.
[21] PEETERS, Toine, SNELDERS, Stephen, Op.Cit., p. 382.
[22] PEETERS, Toine, SNELDERS, Stephen, Ibid., p. 390.
[23] PEETERS, SNELDERS, Ibid., p. 394.